Dataset Information

Genetic association with ERAP1 in psoriasis is confined to disease onset after puberty and not dependent on HLA-C*06.

ABSTRACT: HLA-C remains the strongest susceptibility candidate gene in psoriasis. Evidence for interaction between HLA-C and endoplasmic reticulum aminopeptidase 1 (ERAP1) confined to individuals carrying the HLA-C risk allele was recently reported. Psoriasis displays wide variation, and genetic heterogeneity is likely to contribute to clinical diversity. Age at disease onset is a putative discriminator, and separating psoriasis into early- (<40 years) and late-onset disease has been useful. To sharpen the age-dependent phenotype, we compared genotypes for ERAP1 (rs26653, rs30187, and rs27524) and HLA-C*06:02 in healthy controls and cases stratified for onset of psoriasis at <10, 10-20, 20-40, and >40 years of age. This approach revealed that association with ERAP1 was confined to cases with onset between 10 and 20 years (odds ratio 1.59, 95% confidence interval: 1.28-1.98, P=0.00008) and no association was detected in cases with onset below 10 years, reflecting genetic heterogeneity within the childhood psoriasis population. In contrast to earlier findings, association with ERAP1 was neither dependent on nor interacting with HLA-C*06:02. ERAP1 single-nucleotide polymorphism rs26653, which, to our knowledge, has not previously been reported in psoriasis, is nonsynonymous, has suggestive functional consequences, and herein displays strong association with disease.

SUBMITTER: Lysell J

PROVIDER: S-EPMC3547223 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic association with ERAP1 in psoriasis is confined to disease onset after puberty and not dependent on HLA-C*06.

Lysell Josefin J Padyukov Leonid L Kockum Ingrid I Nikamo Pernilla P Ståhle Mona M

The Journal of investigative dermatology 20120830 2

HLA-C remains the strongest susceptibility candidate gene in psoriasis. Evidence for interaction between HLA-C and endoplasmic reticulum aminopeptidase 1 (ERAP1) confined to individuals carrying the HLA-C risk allele was recently reported. Psoriasis displays wide variation, and genetic heterogeneity is likely to contribute to clinical diversity. Age at disease onset is a putative discriminator, and separating psoriasis into early- (<40 years) and late-onset disease has been useful. To sharpen th ...[more]

PMID: 22931917

Similar Datasets

Project description:ImportancePrevious research showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis but consisted mostly of small (and sometimes inconclusive) cohort studies.ObjectiveTo assess whether HLA-C*06:02 status is associated with a differential response to ustekinumab therapy in patients with psoriasis through a systematic review and a meta-analysis of available data.Data sourcesA comprehensive search was conducted using MEDLINE, Embase, the Cochrane Library, Web of Science, and gray literature sources. Databases were searched from January 1, 2000, to May 14, 2018. Search strategies included terms and synonyms for psoriasis, HLA-C, and ustekinumab. Languages were restricted to English, French, German, and Dutch.Study selectionStudies were included if they reported the association between HLA-C*06:02 status and 75% improvement in Psoriasis Area and Severity Index (PASI75) response to ustekinumab therapy in patients with plaque psoriasis after 6 and/or 3 months of treatment. Randomized clinical trials and observational studies were included. Screening and selection were performed independently by 2 reviewers.Data extraction and synthesisHLA-C*06:02 genotype status and PASI75 response rates were extracted by 2 reviewers. Data were pooled using random-effects models. Heterogeneity was assessed using the τ2 and I2 statistic. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed.Main outcome and measureThe primary outcome was the risk difference of achieving PASI75 after 6 months of ustekinumab therapy between HLA-C*06:02-positive and HLA-C*06:02-negative patients.ResultsA total of 8 studies were reviewed; 1048 patients were included for meta-analyses, and 937 patients were included for the primary analysis of PASI75 response after 6 months of treatment. Random-effects meta-analysis showed a risk difference of 0.24 (95% CI, 0.14-0.35; P < .001) in favor of HLA-C*06:02-positive patients. The median PASI75 response rate in the HLA-C*06:02-positive group was 92% (pooled, 89%; range, 62%-98%). For HLA-C*06:02-negative patients, the median response rate was 67% (pooled, 62%; range, 40%-84%). Substantial heterogeneity may have been present, with an I2 of 82%.Conclusions and relevanceThe meta-analysis showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis. Although HLA-C*06:02-positive patients had high PASI75 response rates after 6 months, the PASI75 response rate was also high in the HLA-C*06:02-negative group. There appears to be no rationale for excluding patients from ustekinumab treatment based on a negative HLA-C*06:02 status.

Dataset Information

Genetic association with ERAP1 in psoriasis is confined to disease onset after puberty and not dependent on HLA-C*06.

Publications

Genetic association with ERAP1 in psoriasis is confined to disease onset after puberty and not dependent on HLA-C*06.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets